Inhibition of lipolysis in hamster adipocytes by the cation ionophor X537A
Journal of Cyclic Nucleotide Research 5(4): 327-338
ISSN/ISBN: 0095-1544 PMID: 227946 Accession: 005704717
The effects of the lipophylic ionophore X537A on lipolysis and accumulation of c[cyclic]AMP in isolated hamster epididymal adipocytes is reported. X537A inhibited lipolysis activated with norepinephrine, isoproterenol, dibutyryl cAMP or theophylline but failed to influence basal lipolysis. The minimum effective concentration of X537A required to inhibit lipolysis was between 1 and 3 .mu.g/ml; at a concentration of 10 .mu.g/ml, X537A inhibited lipolysis by approximately 50%. The antilipolytic effect of X537A is not due to decreased formation of cAMP because the accumulation of cAMP in response to isoproterenol or theophylline was significantly potentiated in the presence of the ionophore. Most of the additional cAMP that accumulated in the presence of X537A was intracellular, the distribution of cAMP between cells and incubation medium not being influenced by X537A. The basal activity of cAMP dependent protein kinase or the activity in the presence of isoproterenol or theophylline was not influenced by X537A. The effects of X537A on lipolysis and on accumulation of cAMP persisted in the absence of extracellular Ca, but adipocytes that were preincubated in a Ca free media containing 1.0 mM EGTA [ethylene glycol-bis(.beta.-amino ethyl ether)N,N,N'-tetraacetic acid] failed to respond to X537A with an increase in cAMP levels. Apparently X537A inhibits lipolysis by uncoupling cAMP accumulation from activation of triglyceride lipase by a mechanism unrelated to activation of protein kinase.